European Journal of Clinical Pharmacology

, Volume 21, Issue 1, pp 77–81

Protein binding of drugs in plasma, interstitial fluid and tissues: Effect on pharmacokinetics

  • E. M. Faed
Original

Summary

Drug binding in the interstitial fluid as well as in the plasma must be taken into account when considering the pharmacokinetics of drugs which are highly bound to plasma proteins and have a relatively small apparent volume of distribution (V). The half-life and apparent volume of distribution of such a drug can be affected significantly by changes in the extent of binding of the drug in both the plasma and the interstitial fluid. An alteration in the fraction of drug in the tissues which is unbound will primarily affect the pharmacokinetics of drugs which have a relatively large apparent volume of distribution. The effect of changes in the plasma free fraction of drug (fP) on tissue binding can be deduced from a plot of fP versus V, but not from a plot of fP versus β.

Key words

protein-binding tissue binding interstitial fluid plasma protein volume of distribution half-life 

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References

  1. Gibaldi M, Levy G, McNamara PJ (1978) Effect of plasma protein and tissue binding on the biological half-life of drugs. Clin Pharmacol Ther 24: 1–4Google Scholar
  2. Gibaldi M, McNamara PJ (1977) Tissue binding of drugs. J Pharm Sci 66: 1211–1212Google Scholar
  3. Gibaldi M, McNamara PJ (1978) Apparent volumes of distribution and drug binding to plasma proteins and tissues. Eur J Clin Pharmacol 13: 373–378Google Scholar
  4. Gillette JR (1971) Factors affecting drug metabolism. Ann NY Acad Sci 179: 43–66Google Scholar
  5. Gleichmann W, Backmann GW, Dengler HJ, Dudeck J (1973) Effect of hormonal contraceptives and pregnancy on serum protein pattern. Eur J Clin Pharmacol 5: 218–225Google Scholar
  6. Gugler R, Shoeman DW, Huffman DH, Cohlmia JB, Azarnoff DL (1975) Pharmacokinetics of drugs in patients with nephrotic syndrome. J Clin Invest 55: 1182–1189Google Scholar
  7. Jensen H, Rossing N, Andersen SB, Jarnum S (1967) Albumin metabolism in the nephrotic syndrome in adults. Clin Sci 33: 445–457Google Scholar
  8. Jusko WJ, Gretch M (1976) Plasma and tissue binding of drugs in pharmacokinetics. Drug Metab Rev 5: 43–140Google Scholar
  9. Levy G, Lai C-M, Yacobi A (1978) Comparative pharmacokinetics of coumarin anticoagulants XXXII: Interindividual differences in binding of warfarin and dicoumarol in rat liver and implications for physiological pharmacokinetic modelling. J Pharm Sci 67: 229–231Google Scholar
  10. Øie S, Tozer TN (1979) Effect of altered plasma protein binding on apparent volume of distribution. J Pharm Sci 68: 1203–1205Google Scholar
  11. Plantin L-O, Ahlinder S, Norberg R, Birke G (1971) The distribution of proteins between intra- and extravascular spaces in health and disease. Acta Med Scand 189: 309–314Google Scholar
  12. Tillement J-P, Lhoste F, Giudicelli JF (1978) Diseases and drug protein binding. Clin Pharmacokinet 3: 144–154Google Scholar
  13. Wagner JG (1971) Biopharmaceutics and Relevant Pharmacokinetics, p 260. Drug Intelligence Publications, Hamilton, IllinoisGoogle Scholar
  14. Wilkinson GR, Shand DG (1975) A physiologic approach to hepatic drug clearance. Clin Pharmacol Ther 18: 377–390Google Scholar
  15. Yacobi A, Lai, C-M, Levy G (1977) Comparative pharmacokinetics of coumarin anticoagulants XXXI: Effect of plasma protein binding on distribution kinetics of dicoumarol in rats. J Pharm Sci 66: 1741–1743Google Scholar
  16. Yacobi A, Levy G (1975) Comparative pharmacokinetics of coumarin anticoagulants XIV: Relationship between protein binding, distribution, and elimination kinetics in rats. J Pharm Sci 64: 1660–1664Google Scholar
  17. Yacobi A, Levy G (1979) Effect of serum protein binding on sulfisoxazole distribution, metabolism, and excretion in rats. J Pharm Sci 68: 742–746Google Scholar

Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • E. M. Faed
    • 1
  1. 1.MRC Toxicology Research UnitUniversity of Otago School of MedicineDunedinNew Zealand

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